Marcello Lippi's Chinese champions scored all their goals after half-time to stun their hosts, who now have a mountain to climb in the second leg of the semi-final next week.
Kashiwa had been unbeaten in this year's continental campaign and led at the break through Jorge Wagner's 10th-minute opener.
But Evergrande took control in the second half with Muriqui twice on target.
The Brazilian levelled the scores on 58 minutes and, after Dario Conca (67) and Elkeson (79) put Evergrande out of sight, Muriqui completed a stunning second half in stoppage-time.
FC Seoul will take a 2-0 advantage into the second leg of their tie against Esteghlal.
Dejan Damjanovic fired the Korean side ahead on 38 minutes before Ko Yo-han ensured a solid home win a minute after half-time.
Wednesday's AFC Champions League Semi-final Results
Kashiwa Reysol 1-4 Guangzhou Evergrande
FC Seoul 2-0 Esteghlal